Analogs of the thyroid hormones, thyroxine and 3,5,3'-triiodothyronine, are synthesized in order to define specific structural, functional and conformational requirements for hormone-like or hormone antagonist effects. Biological testing systems include the rat antigoiter assay, binding studies to thyroxine-binding globulin and prealbumin, binding to rat liver cell nuclei and the solubilized thyroid hormone receptor protein, and the stimulation of amino acid uptake by the rat thymocyte. Molecular orbital calculations are used to establish conformational characteristics and the predicted nature and strength of specific binding interactions.